Project Summary/Abstract The subjective experience of loss of control (LOC) over eating, regardless of the amount of food consumed, is commonly reported by youth, particularly among those prone to excess weight. Youth with LOC eating are at increased risk for weight and fat gain, as well as metabolic syndrome. Preliminary research suggests that youth with LOC eating have elevated chronic inflammation, which has been implicated in the development of deleterious health outcomes including metabolic syndrome, diabetes mellitus, and cardiovascular disease. Elucidating behaviors that promote chronic inflammation, above and beyond the contribution of excess body weight, is crucial to developing interventions to prevent the associated adverse health outcomes. Affect regulation theories propose that LOC eating occurs in response to psychological stressors. Indeed, psychological stressors have been shown to increase concentrations of pro-inflammatory factors, thereby modifying the immune response. Frequent psychological stressors that activate the immune response may lead to changes in cytokine secretion patterns and receptor regulation, reducing the capacity to respond to anti-inflammatory signals and exacerbating stress-related disease outcomes. Therefore, it can be theorized that the inflammatory response to stress partly mediates the relationship between acute psychological stressors and adverse health outcomes in vulnerable individuals. However, little is known about the relationship between LOC eating and physiological reactivity to stress among youth. Therefore, we will examine the effect of an acute laboratory stressor on inflammatory markers (IL-1?, IL-6, CRP) and determine whether the inflammatory response to stress mediates the relationship between LOC eating and components of the metabolic syndrome. One hundred-fifty adolescents (12-17 years) with and without reported LOC eating of all weight strata will be studied, and components of the metabolic syndrome will be assessed. During a laboratory visit, participants will undergo a psychological stress task, during which measures of salivary inflammation will be repeatedly collected, from baseline up to 90-minutes post-stressor. We hypothesize that youth with LOC eating will have elevated salivary inflammation at baseline, have a larger increase in salivary inflammation in response to stress, and will have a prolonged elevation of inflammatory markers post-stressor compared to youth without LOC eating. It is further expected that the inflammatory response to stress and recovery will mediate the relationship between LOC eating and components of the metabolic syndrome. The application will provide multidisciplinary training in the conceptual and technical skills needed to carry out this study. The innovative integration of acute psychological stress, aberrant eating, inflammation, and physical health will elucidate the relationship between these variables, as identifying mechanisms through which adverse health outcomes occur may provide a pathway for novel pediatric prevention and intervention programs.